Reduced 11 beta-hydroxysteroid dehydrogenase activity in patients with thenephrotic syndrome

Patients with the nephrotic syndrome (NS) exhibit abnormal renal sodium ret ention which cannot completely explained by a secondary hyperaldosteronism due to reduced renal perfusion. As an alternative mechanism to explain this phenomenon we postulate a cortisol-mediated mineralocorticoid effect as a consequence of a reduced activity of 11 beta-hydroxysteroid dehydrogenase ( 11 beta-HSD). A down-regulation of 11 beta-HSD, i.e. of the shuttle of acti ve to inactive glucocorticosteroids, has been shown to cause mineralocortic oid effects. Therefore we investigated the activity of 11 beta-HSD by measu ring the urinary ratio of (tetrahydrocortisol + 5 alpha-tetrahydrocortisol) /tetrahydrocortis [(THF+5 alpha-THF)/THE] by gas-chromatography in 29 NS pa tients with biopsy-proven glomerulonephritis and 29 healthy control subject s. The ratio of (THF+5 alpha-THF)/THE was higher in NS patients (median 1.4 9, range 0.45-4.07) than in the control subjects (0.98, 0.60-1.36; p<0.01). This ratio was increased as a consequence of a decreased urinary excretion rate of the cortisone metabolite, THE. The present data indicate that a re duced activity of 11 beta-HSD is a new mechanism contributing to the exagge rated sodium retention in patients with the NS.